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Biomedical subjects

J R Krause

Publications and source records attributed to J R Krause.

At least 55 records · Page 3Linked to original sources

Investigation of cell size and nuclear clefts as prognostic parameters in chronic lymphocytic leukemia.

The importance of the size and morphology of peripheral blood lymphocytes has been controversial as prognostic indicators in chronic lymphocytic leukemia (CLL). This study was initiated to specifically examine cell size and morphology with respect to presence or absence of nuclear clefts and the relative importance to survival. Eighty-seven cases of CLL that had not been previously treated were examined. Cleaved cells were considered present in significant numbers when they exceeded 5% of the circulating lymphocytes. Prognosis was not statistically significant when cell size and nuclear clefts were examined individually and in combination. This study confirms that clinical staging is the significant prognostic predictor irrespective of cell size and/or nuclear configuration.

Adult↗

Prolymphocytic transformation of chronic lymphocytic leukemia. A report of three cases and review of the literature.

Three cases of prolymphocytic transformation of chronic lymphocytic leukemia (PLL-trs CLL) are described, and a review of the literature yields 15 additional cases. PLL-trs CLL may be recognized when two populations of cells are present and the number of prolymphocytes are greater than 15% admixed with the small round lymphocytes of CLL. Surface immunoglobulin intensity appears to be greater on the prolymphocytes than on the small lymphocyte in the same case, suggesting a clonal differentiation. At the time of transformation, the spleen is generally larger than at the time of diagnosis of CLL, and lymphadenopathy is variable. Transformation is thought to be associated with increasing refractoriness to treatment and shorter survival, although most of the deaths occurred in clinical Stages III and IV, known to have a poor prognosis. Similar features between PLL-trs CLL and so-called de novo PLL also suggest an evolutionary process. However, additional morphologic and immunologic studies in transforming CLL cases are necessary to answer this question.

Aged↗

Terminal deoxynucleotidyl transferase activity in acute leukemia: a study of 100 cases comparing an immunoperoxidase (PAP) vs immunofluorescent method.

A comparison between the immunofluorescent (IF) method for terminal deoxynucleotidyl transferase (TdT) activity and the immunoperoxidase (IP) method by peroxidase-anti-peroxidase (PAP) technique was done for 100 cases of acute leukemia. For the acute lymphoblastic leukemias (ALL) there was agreement in 93% of the cases. However, the IP method detected 51/55 (93%) TdT+ cases versus 47/55 (85%) by the IF method. For the acute nonlymphocytic leukemias (ANLL), there was an agreement in 89% of the cases. The IP method detected 8/36 (22%) TdT-positive cases while IF detected 4/36 (11%) positive cases. If a figure of 10% TdT+ cells is considered significant in the marrow of the ANLLs, then the IP method would detect eight additional cases for a total of 16/36 (44%) TdT+ cases. This latter figure questions the ability of the IP TdT assay as a single test adequately to determine the lineage of a cell line. It may be rather that TdT is a marker that is expressed in a stem cell.

Acute Disease↗

Morphometric study of megakaryocytes size and prognosis in adults with acute non-lymphocytic leukemia.

Morphometric analysis of megakaryocyte cellular and nuclear size in bone marrow biopsies of 28 cases of acute non-lymphocytic leukemia at diagnosis and 15 controls was performed. Median megakaryocyte cell diameter, median area, and perimeter were less than 95% control range (less than 18.5 microns, less than 263 microns2, less than 64 microns) in 5/5 of induction failures. Attainment of complete remission was significantly greater in those with median megakaryocyte diameter greater than or equal to 18.5 microns (p less than 0.01), median area greater than or equal to 263 microns (p less than 0.001) and perimeter greater than or equal to 64 microns (p less than 0.001). Prolonged complete remission was correlated with normal megakaryocyte size with the median megakaryocyte area, median diameter, and perimeter within or greater than the reference range (greater than or equal to 18.5 microns, greater than or equal to 263 microns2, greater than or equal to 64 microns, p less than 0.05) in 6/7 cases with continuous remissions greater than 3 yr. Measurements of megakaryocyte size may be useful in predicting induction failure and possibly the likelihood of prolonged complete remission in adults.

Acute Disease↗

Phagocytic macrophages in the bone marrow biopsies of children with Hodgkin's disease.

Phagocytic macrophages in bone marrow aspirates have been described as normal and are frequently observed in autoimmune disorders. They are rarely seen in bone marrow biopsies. We observed phagocytosis of leukocytes and nuclear debris by macrophages in the bone marrow biopsies in 20 of 26 children with Hodgkin's disease before therapy. In contrast, phagocytic activity was present in only 1 of 16 children with solid tumors and 4 of 17 children receiving chemotherapy for neoplasia other than Hodgkin's disease. In all groups the marrow was not directly involved by tumor. The presence of macrophage activity did not correlate with clinical stage or histological type of Hodgkin's disease or with the peripheral blood count. Its increased frequency in patients with Hodgkin's disease may reflect abnormal macrophage function in those patients.

Adolescent↗

Secondary non-hematopoietic cancers arising following treatment of hematopoietic disorders.

Aggressive treatment of neoplastic disease has resulted in improved survival and, in some cases, cure of the primary malignancy. One of the most serious complications of such anticancer treatment has been the occurrence of an acute leukemia (primarily non-lymphocytic) several years after the successful treatment of the original neoplasm. Within the last 12 years, the authors have encountered 26 individuals who developed a second non-hematopoietic malignancy (excluding skin cancers) following primary aggressive treatment of a hematopoietic malignancy. All individuals had been treated with chemotherapy (24 of 26 with alkylating agents). The secondary tumors included lung (7), colon (6), gastric (4), bladder (3), esophageal (3), rectal (2) and pancreatic (1) tumors. The average time to development of the second malignancy in this series was 55.1 months, and the survival period following the diagnosis of the second malignancy averaged 7.3 months. It may be that aggressive anticancer treatment may be responsible for the emergence of a host of second non-hematopoietic carcinomas in addition to the now well established association with induced acute non-lymphocytic leukemias.

Adult↗

Bone marrow biopsy findings in angioimmunoblastic lymphadenopathy.

Bone marrow biopsies from 13 cases of lymph-node-biopsy-proven angioimmunoblastic lymphadenopathy (AILD) were studied. Eight cases (62%) showed a characteristic 'granulomatoid' lymphoreticular infiltrate composed of a mixture of lymphocytes, epithelioid histiocytes, immunoblasts, plasma cells and eosinophils in varying proportions. Proliferation of blood vessels, although much less prominent than that described in lymph nodes, and a marked degree of reticulin fibrosis were also noted. The pattern of involvement was mainly focal and rarely diffuse. The foci were either single or multiple, and were distributed throughout the marrow but were only rarely paratrabecular. The associated haematopoietic marrow findings were nonspecific regardless of degree of bone marrow involvement. The histopathology of involved bone marrows in angioimmunoblastic lymphadenopathy is such that in some cases it should strongly suggest the diagnosis even in the absence of a prior definitive lymph node biopsy. Differentiating features from other disorders that might be confused with AILD are discussed. Survival rate was adversely affected by bone marrow involvement.

Aged↗

Bone marrow response to chemotherapy in acute lymphocytic leukaemia and acute non-lymphocytic leukaemia.

Histopathologic changes in core bone marrow biopsies were reviewed in 33 patients with acute leukaemia during chemotherapy to compare the changes in acute lymphocytic leukaemia (ALL) with acute non-lymphocytic leukaemia (ANLL). Cellular, stromal, and bony changes were evaluated with regard to diagnosis and time of biopsy from initiation of chemotherapy. A significant difference was noted in the plasma cell response. Plasmacytosis was present in 19/19 cases of ANLL, but in only 2/14 cases of ALL. Cellular depletion was also significantly less frequent in ALL. Other stromal changes such as haemorrhage, dilatation of sinusoids and fat regeneration, as well as osteoblastic bone activity occurred with similar frequencies in all cases of treated acute leukaemia. Fibrosis, necrosis, and serous atrophy were uncommon. Differing chemotherapeutic regimens and differing patient ages were both correlated with the plasma cell response, but not with the difference in cellular depletion.

Acute Disease↗

Occurrence of three cases of carcinoma in individuals with Crohn's disease treated with metronidazole.

Controversy exists regarding the safety of metronidazole. Experimental studies have suggested both a carcinogenic and mutagenic effect in animals. In women treated with metronidazole for trichomoniasis which involves low dosages and short time periods, no carcinogenic effect was noted. Metronidazole is also used in the treatment of Crohn's disease which involves larger dosages over longer periods of time. The authors have recently encountered three individuals with Crohn's disease who were treated with large doses of metronidazole and who developed a malignancy [breast (two) and cholangiocarcinoma] at a rather young age (32, 31, and 27 years, respectively). Whereas this association based on three cases is not per se incriminatory or even suggestive, nevertheless, the cases are unusual and we urge prospective and long-term follow-up studies on individuals being treated with large doses of metronidazole over prolonged periods of time. Metronidazole (Flagyl) was introduced into The United States in the 1960's for the treatment of trichomoniasis (1). The conditions for which this drug is indicated and has been used have expanded to include such diverse entities as amebiasis (2), brain abscess (3), and Crohn's disease (4). A controversy exists regarding the safety of this drug (5, 6). Experimental studies have shown that metronidazole is both carcinogenic and mutagenic (7-9). However, a recent study (10) cited lack of evidence for a carcinogenic effect with the use of metronidazole in women treated for trichomoniasis. In the past 1 1/2 years we have encountered three unusual cases involving individuals who were treated with large doses of metronidazole for Crohn's disease and who developed a malignant neoplasm at a relatively young age. The features of these three cases are the subject of this report.

Adenoma, Bile Duct↗

Aplastic anemia terminating in hairy cell leukemia. A report of two cases.

Aplastic anemia and hairy cell leukemia (HCL) characteristically present with a pancytopenia, and several reports have described HCL as mimicking aplastic anemia. Usually the bone marrow core biopsy will easily differentiate these entities, as aplastic anemia is hypocellular, and HCL has a mononuclear cellular infiltrate with increased reticulin. In the experience of the author with 67 cases of HCL, two cases have been encountered that clinically and morphologically appeared to be aplastic anemia before terminating in HCL 23 months and 15 months later, respectively. The clinical courses are described for these two individuals. Hairy cell leukemia may not only mimic aplastic anemia, but on rare occasions, aplastic anemia may actually precede hairy cell leukemia.

Adult↗

Leukemia with multiple phenotypic expressions.

A patient is described who, during a three-year illness, exhibited multiple phenotypic expressions of leukemia. She was diagnosed initially as having acute lymphoblastic leukemia (ALL) followed by chronic myelogenous leukemia (CML) one and a half years later. Subsequent blast transformations were lymphoblastic, but preterminally, a myeloblastic transformation occurred. These later leukemias probably were not chemotherapy induced, because a review of her initial work-up revealed the presence of a smaller G group chromosome in 1 of 20 metaphases examined. Her clinical course also differs from the CML that presents in lymphoid blast crisis because the Philadelphia chromosome only was emerging at that point. This case illustrates the interrelationships of the various leukemias and supports the hypothesis that a totipotent stem cell may undergo leukemic transformation resulting in variable and simultaneous expressions.

Adult↗

Heterogeneous acute leukemias.

We have reported two cases of Philadelphia-chromosome-negative acute leukemia with heterogeneous populations of leukemic cells and reviewed six cases from the literature. The cases were identified by several methods, including morphology, cytochemistry, enzymatic analysis, cytogenetic analysis, and electron microscopy. Predisposing factors were probably present in three cases and may partially account for the seemingly increasing incidence, as has been the experience with other secondary leukemias. The prognosis was variable, but most of the complete remissions were seen only when lymphocytic and nonlymphocytic antileukemic chemotherapeutic regimes were used. The occurrence of these unusual acute leukemias strongly supports the concept of a lymphoid-myeloid stem cell.

Acute Disease↗

Hemoglobin concentration and aerobic work capacity in women following induced erythrocythemia.

The effect of induced erythrocythemia on hemoglobin concentration ([Hb]) and aerobic work capacity was determined for nine women. Cycle tests were performed at prereinfusion (T1), 2 days after a placebo infusion (T2), 2 days postreinfusion of 334 ml of red blood cells (T3), 8 days postreinfusion (T4), and 14 days postreinfusion (T5). T1 and T2 responses did not differ, negating a placebo effect. [Hb] increased from 12.7 g X dl at T1 to 14.7 g X dl at T3 and then remained constant at T4 and T5. Hematocrit increased from 38.1% at T1 to 44.9% at T3 and then remained constant at T4 and T5. Submaximal O2 uptake (VO2) and stroke volume (SV) did not change from T1 through T5. Submaximal cardiac output (Q) and heart rate (HR) decreased from T1 to T3 and then remained constant at T4 and T5. Arteriovenous O2 difference increased from T1 to T3 and then remained constant at T4 and T5. Maximal VO2 was greater at T3 (2.65 l X min-1), T4 (2.66 l X min-1), and T5 (2.60 l X min-1) than at T1 (2.41 l X min-1). Physical work capacity was greater at T3 (10,740 kg X m), T4 (10,980 kg X m), and T5 (10,380 kg X m) than at T1 (8,747 kg X m). Maximal values for Q, HR, and SV were unchanged from T1 through T5. At maximum, arteriovenous O2 difference and Hb flow rate increased from T1 to T3 and then remained constant at T4 and T5. The greater postreinfusion [Hb] improved O2 transport capacity and appeared to regulate circulatory responses.

Adult↗

Paroxysmal nocturnal hemoglobinuria and acute non-lymphocytic leukemia. A report of three cases exhibiting different cytologic types.

Three individuals with paroxysmal nocturnal hemoglobinuria (PNH) developed acute non-lymphocytic leukemia (ANLL) as a terminal event. The cytologic types were different in each case suggesting a transformation that may involve a pleuripotent stem cell. Eight previous cases of PNH terminating in acute leukemia have been reported which have also been ANLL in type. Whether PNH should be considered a myelodysplastic or myeloproliferative disorder remains to be seen. PNH has been considered a clonal disorder with several populations of erythrocytes being present. Cytogenetics in the current cases failed to reveal any karyotypic abnormalities during the time PNH was present. However, an abnormal clone appeared in two cases during the time leukemia supervened. Additional studies of PNH as a postulated clonal disorder may provide interesting knowledge for this uncommon disorder.

Acute Disease↗

An appraisal of the value of the bone marrow biopsy in the assessment of proliferative lesions of the bone marrow.

The diagnostic value of the bone marrow needle biopsy has proved impressive in a variety of disorders. As a complementary procedure to the aspiration smear it adds an invaluable dimension to the examination of haematopoietic tissue. The procedure is easily learned and safe and should be utilized routinely in haematological practice. The usefulness of the bone marrow biopsy is examined in assessing proliferative lesions of the bone marrow.

Biopsy, Needle↗

Acute leukemia following a malignant teratoma in a child with Klinefelter's syndrome: case report and review of secondary leukemias in children following treatment of a primary neoplasm.

A case of Klinefelter's syndrome with the development of a mediastinal teratocarcinoma is reported suggesting that the association of a gonadotropin-secreting tumor with the XXY chromosomal abnormality may be more than coincidental. Whereas this child appeared to survive the effects of the teratocarcinoma, he succumbed to acute leukemia two years later. This prompted a review of secondary leukemias in children following chemotherapy/radiotherapy for another primary malignancy. These patients responded poorly to treatment of the secondary leukemia with a median survival of about four months. The incidence of secondary leukemias might be expected to be on the rise as increasing numbers of pediatric cancer patients are surviving longer after treatment with agents that are potentially leukemogenic or carcinogenic themselves. Children who have survived cancer and its therapy present special problems and it will be necessary for the pediatrician and practitioner to monitor these children.

Adolescent↗

Chronic idiopathic thrombocytopenic purpura (ITP:) development of acute non-lymphocytic leukemia subsequent to treatment with cyclophosphamide.

Chronic idiopathic thrombocytopenic purpura (ITP) is most often treated successfully with steroids and/or splenectomy. In those who fail to respond with the foregoing treatment, immunosuppressive drugs are sometimes added to the regimen. Cyclophosphamide has been reported heretofore to be effective with a minimum of side effects and complications. However, the use of alkylating agents and the induction of a second malignancy is now well recognized. This report describes three cases of refractory ITP treated with cyclophosphamide who subsequently developed an acute non-lymphocytic leukemia. Cyclophosphamide should be used with discretion in the treatment of chronic idiopathic thrombocytopenic purpura which is a non-neoplastic disorder.

Adult↗